Gonadotropin-releasing hormone (GnRH) is secreted in hypothamaus and transmitted to pituitary, where the hormone is specifically linked to a high affinity receptor which exists on the cell membrane of pituitary to interact with each other. GnRH is secreted in the hypothamaus by means of a pulse pattern. In fact, every normal physiological synthesis and secretion-related reactions are involved in pulse mode reaching a receptor (Belchetz P E et al., Science 202, 631-633, 1978).
Human GnRH receptor (GnRH-R) gene is composed of three exons and two introns (Fan N C et al., Moll. Cell. Endocrinol. 107, R1-R8, 1995), which enables various splicing or transmission of variants, suggesting the diversity in its function. GnRH and GnRH-R are found in major lymphatic organs or immune cells including lymphocytes (Standaert F E et al., Biol. Reprod., 46, 997-1000, 1992). GnRH-R is found in not only testis or ovary (Botte M C et al., J. Endocrinol. 159, 179-189, 1998), in addition to pituitary, but also pituitary adenoma secreting growth hormone, progesterone or thyroid-stimulating hormone (Rosa S L et al., Virchows Arch., 437, 264-269, 2000). Although the physiological functions of GnRH-R in the pituitary of the central nervous system (CNS) have been well known, the other functions in other regions have been hardly disclosed.
Myelin is an extended cell membrane of a fat-rich oligodendrocyte or Schwann cell covering the axon of a neuron, which has a function of transmitting nerve impulse by action potential to other neurons or muscle junctions of motor neurons. Considering the ratio between major components of myelin, the percentage of lipid is characteristically high over protein. In particular, protein takes 30% of the total weight of dried myelin found in human or rodent brains and the remaining 70% is consisted of lipid components. Myelin found in CNS is composed of 28% cholesterol, 28% glycolipid and 43% phospholipids. Glycolipid and sphingolipid take 35% of the total lipid.
It has been known that myelin in CNS has more than 40 enzyme activities, based on which it is understood that the function of myelin as an electric insulator is characterized by an active metabolism resulted by a unique enzyme activity. Besides, the membrane of myelin harbors muscarinic receptors (Larocca J N et al., J. Neurosci., 7, 3863-3876, 1987) or G-protein receptors (Larocca J N et al., J. Neurochem., 57, 30-38, 1991), indicating that myelin is capable of transmitting a signal.
Myelin is found in rather white matter than gray matter of CNS, which are confirmed by staining methods such as Busch's method, Loyez's method and Luxol fast blue method, etc. It is also possible to use a protein component of myelin such as 2′,3′-cyclic nucleotide 3′-phosphodiesterase (CNP), myelin-associated glycoprotein, myelin basic protein, galactocerobroside, myelin oligodendrocyte glycoprotein and proteolipid protein, as a marker for searching myelin with immunohistochemical staining (Trapp B D et al., Cell biology of myelin assembly, In: Myelin biology and Disorders, edited by Lazzarini R A et al., p. 29-55, Elsevier Academic Press, Amsterdam, 2004; Sospedra M. and Martin R, Ann. Rev. Immunol., 23, 638-747, 2005).
Examples of the use of a specific protein as a searching marker include Korean Patent No. 10-2005-0052754 which describes the use of PrxII protein as a marker for searching vascular endothelial cells and a composition for searching vascular endothelial cells containing an antibody against PrxII protein. However, the use of GnRH-R as a marker for searching a specific region or a specific material, especially myelin, has not been reported in any scientific literature, yet.
The present inventors observed GnRH-R in the same region where myelin is found, and then suggested the usability of GnRH-R as a new marker for searching myelin. The present inventors further completed the invention by confirming that GnRH-R can be effectively used for the treatment of myelin-related diseases including demyelination-related degenerative brain disease.